Posts Tagged ‘enzymes’

Notes on dosage
In this dictionary of drugs, the doses, unless otherwise stated, are average daily doses for adults, and are normally given as divided doses at suitable intervals. An indication is given of those few drugs that are taken as a single daily dose, or where
the dose is based on the surface area of the body expressed as square metres (ml).
When a dose range is indicated, a small initial dose is often followed by gradually increasing doses according to need and response, but with long-acting drugs care must be taken to avoid excessive dosage, as such drugs may then accumulate in the body and have toxic side-effects. It should be noted that the side-effects of a drug may prevent the administration of an optimum therapeutic dose, and a recommended dose is often a compromise between activity and toxicity. The gap is sometimes referred to as the ‘therapeutic window’, and the wider the gap the safer the drug.
Dosage is also influenced by the route of administration, as oral doses are normally larger than those given by intramuscular injection, and the latter are in turn larger than those given intravenously. The weight, age and sex of a patient may also have to be taken into account when assessing dosage. Renal and hepatic
-impairment may require an adjustment of dose, whereas if tolerance to a drug
develops, a larger dose may be required to evoke an adequate response. Dosage
also requires particular care during pregnancy if toxic effects on the fetus are to be avoided and, ideally, no drug should be given in pregnancy unless the need outweighs the risks.
Doses for infants also present problems. Their drug-detoxifying enzyme
systems and renal excretory capabilities are not fully developed although,
paradoxically, they have higher metabolic rates than adults, and so may sometimes require an apparently relatively high dose of a drug.

Doses for the elderly also frequently require modification, as their reduced renal efficiency may cause accumulation of the drug and increase susceptibility to toxic effects, unless reduced doses are given. Elderly patients are, in any case, more susceptible to nephrotic drugs generally. Hepatic disease may also increase drug toxicity as liver enzymes play a major part in drug metabolism, and severe liver disease may give rise to a drug toxicity that might not otherwise occur. Hyperlipidaemic drugs, fusidic acid and some antifungal agents of the ketoconazole type are examples of drugs best avoided in hepatic disease. Multiple therapy may also lead to an increased and not always appreciated incidence of drug toxicity. For further information on these important aspects of drug dosage, a book for nurses on drugs and pharmacology should be consulted.

Controlled drugs
Drugs likely to cause dependence and misuse are referred to as ‘controlled drugs’ (CDs), as they are subject to the strict prescription requirements of the Misuse of Drugs Act, 1971, and are distinguished in this book by a dagger t. They include opium, morphine, heroin (diamorphine), pethidine and other synthetic, potent analgesics/narcotics, dihydrocodeine injection, barbiturates (except intravenous anaesthetics) and amphetamines. Controlled drugs can be supplied only on receipt of a hand-written prescription from the prescriber, giving full details of the patient, the drug, the form and strength of the prescription to be dispensed, and the total amount to be supplied expressed in both words and figures. Certain weak preparations of some controlled drugs, such as Kaolin and Morphine Mixture for diarrhoea, with which misuse is unlikely, are exempt from control, and can be obtained without prescription.

Chemical Intolerance
`To start with, I just used to get this irritation in my throat when I was reading a magazine. Over the years it got much worse, and there was a dreadful burning feeling, not

just in my throat now, but also in my eyes and nose. Sometimes I could scarcely breathe. My doctor said it couldn’t be magazines and diagnosed asthma. Twenty years on, I can’t

look at a magazine, even for a few minutes, and other things affect me now too. If I go in a room with a photocopier running I start to choke and can’t breathe. Whenever I

describe this problem to anyone — apart from the doctor, that is — they almost always say they know someone else who has a similar problem. But the doctors still say that what

happens to me can’t happen.’
Mary has chemical intolerance, which is also known as chemical sensitivity, environmental Illness or idiopathic environmental intolerances. It is a condition that arouses more

passionate controversy than any other described in this book. Many believe that it simply does not exist, or rather that people who claim to have chemical intolerance are

actually victims of psychological problems, which express themselves as physical symptoms. Careful studies show that, while some people with supposed chemical intolerance do

fall into this category, others do not – they have no psychiatric problems, but they do appear to have valid symptoms when exposed to certain synthetic chemicals.
`People with MCS are desperate. They will go to great lengths and do almost anything to find a doctor, anyone, who believes them.’ So speaks one sufferer from MCS (Multiple

Chemical Sensitivity), the most extreme form of chemical intolerance. It is often severely disabling, with symptoms such as exceptional fatigue, nausea, headaches, poor memory

and concentration, dizziness. muscle aches, joint pain, chest pain and digestive problems. Those with MCS react to a very wide range of chemicals, and very often to foods and

food additives as well.
These severely affected patients are a small minority, however, and many more people are like Mary, with sensitivity to just one or two types of chemical exposure. Surveys in

the United States suggest that about 30% of the population are affected in this way. The authors of one such survey note that ‘the widespread idea that chemical sensitivity is a

condition of educated, urban housewives was not supported by our study. The region surveyed was rural… and individuals who reported chemical sensitivity were found in all age,

gender, income, race and employment groups.’
The chemical exposures that are identified as triggering symptoms include:
• perfumes
• pesticides
• cigarette smoke
• paint fumes
• petrol
• exhaust fumes
• cleaning products
• newspaper ink
• plastics, especially those with a strong smell
• glossy paper (e.g. In magazines).
Typical symptoms, in those with sensitivity to just one or two chemical products, are:
• a blocked or runny nose
• sore throat
• irritation of the eyes
• sinus pain and congestion
• headache
• breathlessness and wheezing
• nausea
• skin rashes
• extreme fatigue
• dizziness.
How does chemical intolerance begin?
For some of those with MCS, the problems began with a sudden over-exposure to a toxic chemical, such as a chemical spill, or pesticides from a crop-spraying plane. Others are

first affected by regular doses of pesticide at lower levels, such as spray drift from nearby fields or from a neighbour’s garden. It seems as if, for these people, their inborn

ability to detoxify both natural and manmade toxins is overwhelmed by an unusually heavy exposure, and never fully recovers. Although there have been no systematic studies of

this – it is difficult to imagine how they could be done –the wealth of well-documented cases is convincing. And studies of those exposed to high levels of pesticides in

accidents at work support the idea that this can cause lifelong sensitivity to very small doses of some synthetic chemicals. Sensitivity to alcohol and caffeine usually

increases enormously too.
In some cases, classical allergies also feature in the range of symptoms for those with MCS. If they had an allergic tendency before the accidental exposure to pesticides, this

is especially likely: after the accident, along with chemical intolerance, they have far more pronounced allergic reactions to common allergens.
The loss of tolerance to everyday chemicals may be related to some kind of damage to the enzymes in the liver that carry out the important task of detoxifying toxins that enter

the bloodstream. This detoxification system evolved to deal with natural toxins, such as those in plant foods, and those produced by bacteria living naturally in the gut. These

enzymes can also detoxify the widely used synthetic chemicals, when these are encountered in relatively small amounts, but the enzymes are overwhelmed by large doses.
Chronic Fatigue Syndrome (CFS)
This is a disease that probably has multiple causes rather than a single cause. The main symptom is fatigue that is not relieved by rest. Many people with CFS also have a

slightly raised temperature, problems with concentration and memory, headaches, sore throat and swollen lymph nodes (’swollen glands’). The lymph nodes are part of the immune

system, so this symptom suggests some disturbance of immune function. Other findings, related to immune cells in the blood, also support this idea. However, there are often

minor abnormalities in the brain as well, with some loss of the insulating material around the nerves (myelin).
For many patients, the disease develops in the wake of a viral infection, but for others the origin may be unclear. Whatever the origin of the disease, avoiding synthetic

chemicals is very helpful in many cases. Some sufferers also find an elimination diet helpful (see pp. 194-7). Doctors working in this area say that there is no sharp

demarcation between patients with Chronic
Fatigue Syndrome (CFS) and those with MCS.
Autism
In the search for a cause of autism, many possibilities are being investigated. The consensus now is that there is a genetic predisposition which, when combined with certain

trigger factors, leads to autism.
What are those trigger factors? Some researchers suggest that autistic children have poorly performing detoxification enzymes and are therefore sensitive to synthetic chemicals,

both in food and the environment. The suspicion is that these chemicals affect the developing nervous system.
Other researchers pinpoint food as the culprit. They believe that children who develop autism are affected by exorphins (see p. 76) produced from the proteins in wheat and/or

milk, and that these damage the child’s developing nervous system. There are claims that a dairy-free and gluten-free diet can help, but that it must be ultra-strict to work,

and may need to continue for at least six months before any improvement occurs. You must have your doctor’s approval for this.
Before starting them on such a diet, some doctors also give a course of anti-fungal drugs to those autistic children who have been treated repeatedly with antibiotics. This

combined treatment is reported to have very good effects for some children.
Treatment
Assuming that you really do have chemical intolerance rather than some deep-rooted psychological problem – and you have to be honest with yourself here, because otherwise you

will never get better – then careful avoidance of the offending synthetic chemicals is the only effective treatment. If you have eliminated everything that obviously affects you

and are not much improved, then try tackling common indoor pollutants (see pp. 128-30) as well.
Such measures are of value to some with chemical intolerance but may not be adequate for those most severely affected. If you need to take more radical steps, you may benefit

from the bedding, paints and other household items manufactured for those with chemical sensitivity. Once you reduce the level of synthetic chemicals in your everyday

environment, you may find that you can tolerate occasional exposures much more.
Some doctors recommend taking supplements of vitamins and minerals to speed your recovery. These (especially antioxidants – see p. 206) may be helpful for some people, but be

sure to get nutritional advice from someone with good medical qualifications, rather than a self-styled ‘nutrition therapist’.
Neutralisation therapy (see p. 211) seems to be effective for some people with chemical intolerance, but you will still need to avoid the offending substances. Hyperventilation

(see p. 236) can make chemical intolerance much worse.

Food Intolerance
The comments of those who have recovered from food intolerance after many years of ill-health are always memorable. ‘It’s like getting my life back again,’ said one woman. ‘I had actually forgotten what it felt like to be well,’ said another, ‘the effect of cutting out certain foods was just amazing.’
For most of those with food intolerance, the disease begins very subtly and gradually – first one symptom (persistent and unexplained diarrhoea, perhaps) then, some years later, another (migraine or headaches) and then, when a few more years have passed, another symptom (such as joint pain or muscle aches). Steadily increasing levels of irritability, `fuzzy-headedness’ or inexplicable tiredness may accompany this decline in health.
Most patients have no idea that all these symptoms are connected until they try an elimination diet, and everything clears up at once, quite dramatically. As one former sufferer described it: `Some of the stuff that got better – well, I’d been like that so long I thought it was just the way I was –grumpy and exhausted, and feeling terrible if I didn’t eat meals on time. It was an absolute revelation to feel completely OK again.’
What does ‘food intolerance’ mean?
In this book, food intolerance means any reaction to food where the immune system has no proven central role.
All the people I have described so far have idiopathic food intolerance, which means, food intolerance with no established mechanism – in other words, doctors can’t say exactly how it is caused. This is a highly controversial area.
The definition of food intolerance used in this book means that it also includes metabolic abnormalities, which do have a well-established cause. These are due to defective enzymes (see upper box on p. 75).
The question of what words mean is a key part of the debate over idiopathic food intolerance. At one extreme, you may come across doctors who call this problem ‘food allergy’, using the original meaning of the word ‘allergy’ (see p. 6). (Some of these doctors use terms such as delayed food allergy and masked food allergy, to point up the distinction from true food allergy, but not all do.) Using the word ‘allergy’ in this context causes a lot of aggravation and confusion, so the term ‘food intolerance’ has, for a long time, been widely accepted as a useful one that avoids unnecessary conflict.
You will also hear the term ‘food intolerance’ used to mean idiopathic food intolerance only – this is probably the most common usage. When the term is used in this way, metabolic abnormalities are being thought of as a separate entity altogether.
A new twist has recently been added to this long-standing wrangle over meanings. When mentioning food intolerance in their literature, some of the major medical organisations (those who dispute the very existence of idiopathic food intolerance) now say simply ‘food intolerance e.g. lactase deficiency’. To anyone familiar with this field, it looks suspiciously like an attempt to redefine ‘food intolerance’ so that it means nothing more than ‘metabolic abnormalities’. The idea seems to be that, if you deny a disease a name, it will go away!
In the medical wilderness
The main text of this article is about idiopathic food intolerance, a disease with a distinctly dubious reputation among doctors. Because it is so controversial, few doctors actually look at the evidence that it exists – which is in fact quite strong (see box on p. 77). Such evidence is simply ignored in most of what is written by the major medical organisations debunking idiopathic food intolerance.
This lack of medical recognition is very unfortunate for patients with idiopathic food intolerance, whose debilitating symptoms could be eliminated, rather than simply being treated (usually to little effect) with drugs.
This prejudiced attitude to idiopathic food intolerance also plays into the hands of those offering bogus diagnostic tests and phoney treatments, often at a very high price. These practitioners
– who have moved in to fill the gap left by conventional medicine
– are a considerable part of the problem, helping to give idiopathic food intolerance a bad name.
The waters are muddied even more by the fact that some people who believe themselves to have food intolerance are actually suffering from psychological problems, which they prefer to attribute to food. Many more have picked up on food intolerance as something rather glamorous to suffer from, inspired by all the media reports about food intolerance among celebrities. All these patients are a good source of revenue for the less scrupulous fringe practitioners and are unlikely, therefore, to be discouraged from their beliefs.
Fortunately there are enough conventional but open-minded doctors, often GPs, who have come to realise, through experience with their own patients, that elimination diets have a remarkable curative effect for some people. The ones who benefit are often the doctor’s ‘old faithfuls’ – those with long-term multiple symptoms, who have been referred to innumerable specialists and treated with all kinds of drugs, but who never get much better. The conventional view of such patients is that they have psychological problems that are being expressed as physical symptoms. This may well be true for some – but others have idiopathic food intolerance.
One of our enzymes is missing
Metabolic abnormalities are a distinct type of food intolerance. Unlike other kinds of food intolerance, metabolic abnormalities have a clearly understood cause: an enzyme that carries out a crucial task in the body’s metabolism is either missing or inept. The problem is generally caused by a defective gene and is therefore inherited.
The most common metabolic abnormality is lactase deficiency leading to lactose intolerance (see p. 79) — this may or may not be inherited. Other metabolic abnormalities include:
trehalase deficiency, lack of the enzyme which breaks down a substance in mushrooms and most other fungi, including yeast. galactosaemia, a defect in the enzyme which processes galactose, one of the sugars found in milk (cow’s or human). This is a serious disease and sufferers must avoid milk scrupulously.
fructose intolerance, which is extremely rare. Those affected have an unpleasant taste in the mouth on eating fruit and other sources of fructose, so avoidance is no particular problem.
phenylketonuria, also very rare. Those affected are usually identified early in life, by a routine blood test.
Is it just placebo effect?
Doctors who doubt the very existence of idiopathic food intolerance will say that people who recover on an elimination diet are just experiencing placebo effect — a psychological response that operates with any treatment, whether effective or ineffective, simply because people believe that the treatment will work. But this is to ignore certain facts:
• Placebo effect produces a fairly small improvement in most people — you have to be very suggestible to feel enormously better. By contrast, when people respond to an elimination diet (the standard method for diagnosing idiopathic food intolerance —see p. 194) they usually have a sudden and dramatic improvement.
• Most of those with idiopathic food intolerance have had it for years and tried all sorts of treatments. They have often experienced some small benefit from these, probably placebo effect. When they try an elimination diet, they have a response that is in a completely different league.
• The idea that all the different symptoms are linked has never occurred to many people who try an elimination diet — they are often trying it for just one symptom, and are staggered when everything clears up. Placebo effect relies on expectation.
• Placebo effect doesn’t last very long — it fades over the ensuing weeks and months. Avoiding the culprit food usually produces a lasting improvement for those with idiopathic food intolerance.
Symptoms
The symptoms of idiopathic food intolerance come on slowly after eating the offending food, and the foods to blame are often those eaten very regularly, such as wheat or milk. Consequently, the symptoms from one meal tend to overlap with those from the previous meal and people with idiopathic food intolerance are more-or-less unwell for most of the time. It Is usually not obvious that food is at fault.
All the symptoms of idiopathic food intolerance are common ones that can be caused in other ways. And no two patients have exactly the same set of symptoms.
(As far as doctors are concerned, neither of these attributes gives the disease a respectable air.)
These are some of the symptoms commonly reported:
• headache or migraine
•diarrhoea, sometimes with bloating and wind; this is often diagnosed as irritable bowel syndrome (IBS)
• in children, stomach aches
• occasionally constipation
• nausea and indigestion
• joint pain
• aching muscles
• a constantly runny or blocked nose (this could be perennial allergic rhinitis linked to food – see p. 68)
• glue ear (see p. 29)
• fatigue and a general feeling of vague ill-health.
Asthma and eczema, triggered by specific foods (see p. 68), can also be part of the picture.
In babies, colic is often caused by food intolerance, including foods the mother is eating which come through into the breast milk in tiny amounts (see p. 202).
Less common symptoms include:
• recurrent mouth ulcers
• stomach or duodenal ulcers
• chronic urticaria (see pp. 50-53)
• swelling (angioedema).
The following diseases have also been linked to idiopathic food intolerance in some patients:
• Crohn’s disease
• palindromic rheumatism (intermittent episodes of joint inflammation)
• rheumatoid arthritis.
Psychological problems such as depression, anxiety, or hyperactivity in children can sometimes be due to food (see p. 80) but it is rare for such psychological effects to occur without any physical symptoms.
Remember that every single one of these symptoms and conditions can be caused in some other way. However, the constellation of migraine/headache, joint pain and diarrhoea is highly characteristic of idiopathic food intolerance.
How might intolerance be caused?
No one knows how idiopathic food intolerance is caused. There are probably many factors involved, with a slightly different mix of factors in each patient. This would help to explain why the symptoms are so extraordinarily varied, with no two sufferers exactly alike.
Although symptoms accumulate over the years, some people can in fact pinpoint the moment when their problems began. ‘I had this terrible bout of diarrhoea from eating too much melon. I lived near a farm and they were free, because of a glut, so I just gorged myself on them. Although I was over the diarrhoea in a couple of days, I was never what you’d call “regular” after that, and the least thing would upset me. Eventually the doctor said it was irritable bowel syndrome. When the other problems began, ages afterwards – headaches and hypoglycaemia and fatigue – it seemed like something quite separate. I never associated them in my mind with the diarrhoea.’
Bad diarrhoea can clear the intestines of their beneficial bacteria, known collectively as the gut flora (see p. 204), and this is probably what initiates food intolerance in such cases. Large doses of antibiotics (as are sometimes given before an operation, e.g. a hysterectomy), or prolonged and repeated courses of antibiotics, given for glue ear or acne, can also disrupt the gut flora and lead to food intolerance. A study of hysterectomy patients has shown that antibiotic treatment before the operation tends to result in irritable bowel syndrome – a common symptom of idiopathic food intolerance – afterwards.
A few interesting observations suggest that minor metabolic abnormalities – a defect in certain detoxification enzymes – may sometimes play a part in idiopathic food intolerance. This is especially likely where there is intolerance to food additives, or where there are behavioural symptoms (such as hyperactivity) or symptoms involving the nervous system (such as migraine).
A third factor that could play a part for some patients are food-derived exorphins. These are fragments of proteins (called peptides) produced by the digestion of food proteins. They happen, probably by pure coincidence, to resemble the substances called endorphins that we all produce for ourselves. Endorphins
are our internal painkillers. They modify nerve impulses in the body and brain, reducing sensations of pain, and improving the sense of well-being. The receptors to which they bind are the same receptors that bind morphine and heroin - it is the intensive stimulation of these receptors that makes these drugs so effective.
Food-derived exorphins may sound like the stuff of science fiction, but they have actually been demonstrated in the digestion products of wheat and milk. They may exist for other foods as well. They are nowhere near as strong as morphine, but do seem to improve mood.
These exorphins may explain the strange observation (made repeatedly, by a great number of initially sceptical doctors) that patients with idiopathic food intolerance often eat huge amounts of their offending food, and ‘can’t live without it’. Often they eat the food several times day, sometimes at every meal. With a ubiquitous ingredient like wheat or milk, this is not particularly difficult - wheat cereal and milk for breakfast, a cheese sandwich at lunchtime, pasta with a creamy sauce for supper, a milky drink and biscuits at bedtime.
Any of these abnormalities is likely to be just one factor in a multi-factorial disease.
Diagnosis
Unfortunately there are no simple accurate tests for idiopathic food intolerance. The kind of tests you may see offered commercially (in advertisements in health magazines for example) are very inaccurate, and a waste of money. Consequently, the only way to diagnose idiopathic food intolerance is through an elimination diet, in which you cut out all the foods you commonly eat, and then -if you get better - test them one by one.
It sounds easy but it isn’t, so make sure you read all the instructions for doing the diet before you start (see pp. 194-7). You should also see your doctor and get his or her approval. Some symptoms - such as severe diarrhoea or headaches -should be investigated by conventional methods first, in case there is some serious underlying cause.
The first step in diagnosis is to decide if a food really is the cause of the symptoms, and the second step is to identify the food or foods concerned.
The first step is crucial. One of the problems with the diagnostic tests that are advertised - such as those using samples of hair or blood - is that they begin with the second step. In other words they assume that food is the problem (see p. 93).
When it comes to the second step, remember that although common foods are often the culprits, almost anything that is eaten can cause idiopathic food intolerance. Every patient with this problem is different in the foods they react to.
Treatment
Avoidance of the food is usually the best treatment for idiopathic food intolerance - however most people do not have to avoid their problem foods for ever. After a while - it could be six months or it could be three years - you can usually go back to eating it again, but in moderation. You must never start eating the food in large amounts again, and it is best not to eat it every day - certainly not at almost every meal, which is the usual pattern for cow’s milk and wheat in the Western diet.
If you find the restrictive diet too difficult, you could try desensitisation treatment (see pp. 210-13). This can work very well.
The patients who should avoid the culprit food indefinitely are those with Crohn’s disease and rheumatoid arthritis: a severe and irreversible relapse can occur otherwise.
The evidence
The evidence for idiopathic food intolerance is more substantial than its opponents would have you believe.
One very well-conducted and interesting study involved children with severe migraine who were investigated by a research team at Great Ormond Street Hospital in London. These are children who are very difficult to treat successfully by normal means. On an elimination diet, 88% of those children got better — an astonishing number. Not just their migraine, but all sorts of other symptoms as well, including aching limbs, runny noses, asthma, eczema, diarrhoea, wind, mouth ulcers and hyperactivity. Some of these children also had epileptic fits, and even this symptom cleared up on the diet, recurring when culprit foods were tested.
A notable feature of this study is that, of the five researchers involved, four were deeply sceptical at the outset. Their report notes that they ‘embarked on this study believing that any favourable response, such as that claimed to substantiate the dietary hypothesis, could be explained as a placebo response. The positive double-blind controlled trial… provides clear evidence that a placebo response was not the explanation.’
Other studies with good scientific credentials have demonstrated a role for idiopathic food intolerance in adults with migraine, and for sufferers from irritable bowel syndrome and Crohn’s disease. There are also good studies of individual patients with rheumatoid arthritis and palindromic rheumatism (an episodic form of inflammatory arthritis) who have responded dramatically to avoidance of a particular food. Some of these patients were given several double-blind challenges and showed changes in certain immunological tests, as well as joint symptoms, when challenged with the offending food. This suggests that the immune system could be playing some part in these food reactions.